Dietary supplement containing phospholipid-DHA derived from eggs

ABSTRACT

Described herein are manufactured dietary supplements that contain a phospholipid extract, folic acid, vitamin D, vitamin B 6 , vitamin B 12 , Vitamin E, Vitamin C, iodine, iron, and magnesium. 
     Described herein are manufactured dietary supplements that contain a phospholipid extract that contain phospholipid-DHA.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of nonprovisional U.S. applicationSer. No. 14/562,650 filed Dec. 5, 2014, which claims priority toProvisional U.S. Application No. 62/088,528 filed on Dec. 5, 2014 andProvisional U.S. Application No. 61/912,205 filed on Dec. 5, 2013, whichare hereby incorporated by reference in its entirety.

FIELD

The present disclosure generally relates to a nutritional supplementsproviding phospholipid-docosahexaenoic acid derived from eggs.

BACKGROUND

Polyunsaturated fatty acids have numerous crucial biological functionsin mammals. Moreover, in adult humans, certain polyunsaturated fattyacids have been linked to potentially promoting improved cognitiveability and have been theorized as potential treatments for arthritis,cancer, diabetes, lupus, and psoriasis. Also, certain polyunsaturatedfatty acids have been linked to promoting retinal and brain developmentin fetuses and newborns.

SUMMARY

A manufactured dietary supplement that contains a phospholipid extract,folate, vitamin D, vitamin B₆, vitamin B₁₂, vitamin C, calcium, iron,iodine, and magnesium.

A manufactured dietary supplement that contains a phospholipid extractcontaining phospholipid-DHA.

DESCRIPTION OF THE FIGURES

These and other features, aspects and advantages of the presentdisclosure are better understood when the following detailed descriptionof the disclosure is read with reference to the accompanying drawing, inwhich:

FIG. 1 is a schematic depiction of docosahexaenoic acid metabolism in asubject.

FIG. 2 is a schematic depiction of phosphatidylcholine-docosahexaenoicacid.

FIG. 3 is a schematic depiction ofphosphatidylethanolamine-docosahexaenoic acid.

DETAILED DESCRIPTION

Before the present compounds, compositions, and/or methods are disclosedand described, it is to be understood that the aspects described beloware not limited to specific compounds, synthetic methods, or uses assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularaspects only and is not intended to be limiting.

In this specification and in the claims that follow, reference will bemade to a number of terms that shall be defined to have the followingmeanings:

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “a microparticle” includes one or more microparticles.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not.

As used herein, “subject” refers to a mammal, including a human that isin need of supplementation and/or benefits from the compositions andmethods described herein.

As used herein, “organic” refers to a food that complies with U.S.D.Aregulations set out herein below.

As used herein, the term “rounded” means that an outer periphery of astructure is substantially free of angularity. For example, the outerperiphery of microparticles can have spherical shapes and oval shapesthat are free of angularity and have rounded shapes.

As used herein, the term “about” is used to provide flexibility to anumerical range endpoint by providing that a given value may be“slightly above” or “slightly below” the endpoint without affecting thedesired result.

The disclosure provides various teachings on nutritional supplements.The ingredients, compounds, chemicals that make up the elements of thenutritional supplements may contain vitamins, foods, or other organicmatter that is prone to degradation after formulation in a finishednutritional supplement. It is common practice to formulate a nutritionalsupplement to include an “overage” or an additional amount ofingredient. Any amount of ingredient, compound, or chemicals that iswithin an “overage” of the ranges and amounts claimed and exemplified inthis disclosure would be considered equivalent.

As used herein, a plurality of items, structural elements, compositionalelements, and/or materials may be presented in a common list forconvenience. However, these lists should be construed as though eachmember of the list is individually identified as a separate and uniquemember. Thus, no individual member of such list should be construed as ade facto equivalent of any other member of the same list solely based ontheir presentation in a common group without indications to thecontrary.

Concentrations, amounts, and other numerical data may be expressed orpresented herein in a range format. It is to be understood that such arange format is used merely for convenience and brevity and thus shouldbe interpreted flexibly to include not only the numerical valuesexplicitly recited as the limits of the range, but also to include allthe individual numerical values or sub-ranges encompassed within thatrange as if each numerical value and sub-range is explicitly recited. Asan illustration, a numerical range of “about 1 to about 5” should beinterpreted to include not only the explicitly recited values of about 1to about 5, but also include individual values and sub-ranges within theindicated range. Thus, included in this numerical range are individualvalues such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4,and from 3-5, etc., as well as 1, 2, 3, 4, and 5, individually. Thissame principle applies to ranges reciting only one numerical value as aminimum or a maximum. Furthermore, such an interpretation should applyregardless of the breadth of the range or the characteristics beingdescribed.

The nutritional compositions and methods described herein can comprise,consist of, or consist essentially of the essential elements andlimitations described herein, as well as any additional or optionalingredients, components, or limitations described herein or otherwiseuseful in nutritional formula applications.

The present compositions and methods will now be described more fullyhereinafter with reference to the accompanying drawings in whichexemplary embodiments of the disclosure are shown. However, thesecompositions and methods may be embodied in many different forms andshould not be construed as limited to the representative embodiments setforth herein. The exemplary embodiments are provided so that thisdisclosure will be both thorough and complete, and will fully convey thescope of the disclosure and enable one of ordinary skill in the art tomake, use and practice the teachings of the present disclosure.

Polyunsaturated fatty acids have numerous crucial biological functionsin mammals. For example, in humans, numerous polyunsaturated fatty acidshave been linked to cell membrane synthesis, metabolism, andmaintenance. Moreover, in adult humans, certain polyunsaturated fattyacids have been linked to potentially promoting improved cognitiveability and have been theorized as potential treatments for arthritis,cancer, diabetes, lupus, and psoriasis. Also, certain polyunsaturatedfatty acids have been linked to promoting retinal and brain developmentin fetuses and newborns.

For example, docosahexaenoic acid (“DHA”) is one such polyunsaturatedfatty acid that has been implicated in playing a role in fetus andnewborn development as well as potentially playing a role in maintainingand/or promoting improved human cognitive ability. DHA is a long chainomega-3 fatty acid derived from alpha-linolenic acid having double bondsat its 4, 7, 10, 13, 16, and 19 positions. In humans, DHA is primarilyfound in the brain's grey matter where it functions as a building blockfor membrane glycerophospholipids.

Although polyunsaturated fatty acids such as DHA are known to play animportant role in human cognitive ability, fetus development, andnewborn development, Western diets are often deficient in adequateamounts of these polyunsaturated fatty acids, and individuals oftenresort to polyunsaturated fatty acid supplementation to obtain adequatenutritional amounts of these polyunsaturated fatty acids to potentiallyavoid problems associated with polyunsaturated fatty acid deficiencies.For example, pregnant women and health conscious individuals oftensupplement their diets with fish oil and algae extracts in an attempt toobtain adequate amounts of polyunsaturated fatty acids. Moreover, infantformulas are often supplemented with polyunsaturated fatty acids derivedfrom either of these sources.

Although fish oil and algae extracts may be a source of polyunsaturatedfatty acids, numerous problems exist. For example, fish oil often has anundesirable smell and taste. Due to this problem, numerous fish oilformulations often include taste and smell masking agents. However, mosttaste and smell masking agents never completely mask the “fishy” tasteand smell of these oils. Moreover, these taste and smell masking agentsincrease production costs and the amount of time required to manufactureformulations having fish oil extracts. Thus, in many regards, fish oilsupplementation and production of supplements having these substancesremains undesirable due to these problems. Additionally, fish oil andalgal oil extracts do not have high quantities of DHA in thephospholipid form. And fish oil extracts also contain higher levels oftriglycerides and free fatty acids. The higher levels of triglyceridesand free fatty acids are one of the reasons for the undesirable smelland taste.

In addition, numerous problems exist for DHA derived from these sourcesand other commonly used forms of DHA. For example, DHA derived from fishoil and algae are primarily covalently bonded to triglycerides, andother types of pharmaceutical grade DHA are ethyl ester forms of DHA.Additionally, these extraction techniques increase the amount of freefatty acids and triglycerides. In humans, these forms of DHA requiremultiple steps of metabolic processing to be useful for certainbiological functions. Thus, these forms of DHA are energeticallydisfavored due to the amount of metabolic processing required by asubject's body.

Furthermore, when included in nutritional supplements and formulations,these forms of DHA are susceptible to oxidation, which leads toinstability, decreased efficacy, decreased potency, and potentiallyincreased toxicity when using these forms of DHA. The oxidation is alsowhat contributes to the “fishy smell.” In addition to the problemsmentioned above, the triglyceride and ethyl ester forms of DHA oftencause gastrointestinal problems. Therefore, triglyceride and ethyl esterforms of DHA are often enterically coated in an attempt to reduce DHAoxidation and gastrointestinal problems associated with these forms ofDHA, which further increases production costs and the time required tomanufacture compositions having these substances.

DHA from algae or fish oxidizes (stinks) because it must be broken downto free fatty acid DHA, which is then transported via albumin into theblood. Then the supplement must provide high dosages of DHA to “force”it or push it into blood-brain-barrier (“BBB”) or must be converted inthe liver to lipid form DHA (only a small amount do this). It takes ahigh dosages of PC-DHA to cross the blood brain barrier, which is whycompanies put so much in. Ultimately, the DHA must be metabolized intoPC-DHA in order to be circulating and then go into the BBB. PC-DHA isthe only form that can cross the BBB in significant numbers.

Therefore, it is an object of the disclosure to provide nutritionalcompositions including a stable source of DHA that avoids or reduces theproblems associated with conventional polyunsaturated fatty acidsupplementation. The forms of DHA that are most beneficial fornutritional supplementation for cognitive functions are in thephospholipid form, namely phosphatidylcholine docosahexaenoic acid(“PC-DHA”), phosphatidylethanolamine docosahexaenoic acid (“PE-DHA”),phosphatidylethanolamine-docosahexaenoic acid (“PE-DHA”) andphosphatidylserine docosahexaenoic acid (“PS-DHA”). These phospholipidsare conjugated with a docosahexaenoic acid.

Described herein are nutritional compositions containing phospholipidsand DHA conjugated phospholipids derived from eggs and methods of makingsuch nutritional compositions. These nutritional compositions can beadministered to a subject to promote numerous health benefits, whichinclude, but are not limited to, promoting improved cognitive ability,retinal health, decrease inflammation, and neuronal health. Furthermore,these nutritional compositions can be administered to pregnant womenand/or newborns to further promote brain and retinal development infetuses and newborn children.

Eggs contain many phospholipids and the amount of phospholipids in eggsmay be increased by supplementing the hen's diet with polyunsaturatedfatty acids, particularly omega-3 oils. Eggs contain various omega-3fatty acids. Some of the phospholipids contained in eggs include:phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine,lysophosphatidyl choline, sphingomyelin, lysophosphtidyl ethanolamine,and combinations thereof.

Various phospholipids may be extracted from eggs. This “phospholipidextract” derived from eggs may also be referred to as the raw materialor ingredient for a nutritional supplement. Reference to phospholipidextracts claimed by this disclosure will always be phospholipid extractsderived from eggs. The phospholipids contained in the phospholipidextract include phospholipid-docosahexaenoic acid and otherphospholipids. One form of phospholipid-docosahexaenoic acid isphosphatidylcholine-docosahexaenoic acid, and another form ofphospholipid-docosahexaenoic acid isphosphatidylethanolamine-docosahexaenoic acid, and another form ofphospholipid-docosahexaenoic acid is phosphatidylserine-docosahexaenoicacid. The phospholipid extract may also have some free fatty acids andtriglycerides, however, the extract should preferably have less minimalfree triglycerides and free fatty acids. The extract or raw material mayalso include phosphatidylcholine, phosphatidylethanolamine,phosphatidylserine, lysophosphatidyl choline, sphingomyelin,lysophosphtidyl ethanolamine, and combinations thereof.

The phospholipid extract may sometimes be semi-solid and sticky. It canbe difficult to use in tablet or hard capsule products. The raw materialis often not soluble in oil, and using the material may be impracticalin use in softgel, as it may stick on the mill surface during grinding.

In certain aspects, these nutritional compositions include a body thatencapsulates iron, folate, and an additive, wherein the additive caninclude microparticles. In certain aspects, the microparticles have asubstantially rounded shape and include a core. The core contains theraw material or phospholipid extract, which effectively and efficientlydelivers the phospholipid extract to the subject. The core of themicroparticle may be coated. These microparticles can be incorporatedinto the nutritional composition to improve efficacy of phospholipiddelivery.

In addition, these microparticles can be made by providing amicroparticle core made from a pharmaceutically acceptable material anda or phospholipid extract, then coating the microparticle core with afirst layer, and drying the coated microparticle core, thereby formingthe microparticle for the nutritional composition.

In other aspects the nutritional supplement contains the phospholipidextract without the use of microparticles.

Additional features, aspects and advantages of the disclosure will beset forth in the detailed description which follows, and in part will bereadily apparent to those skilled in the art from that description orrecognized by practicing the teachings of the disclosure as describedherein. It is to be understood that both the foregoing generaldescription and the following detailed description present variousembodiments of the disclosure, and are intended to provide an overviewor framework for understanding the nature and character of thedisclosure as it is claimed. The accompanying drawings are included toprovide a further understanding of the disclosure, and are incorporatedin and constitute a part of this specification.

Nutritional Compositions

Described herein are nutritional compositions that include a bodyencapsulating iron, folate, and an additive, wherein the additiveincludes a microparticle having a core that includes a phospholipidextract and a coating. The body in the nutritional compositionsdescribed herein can include, but is not limited to, a tablet, anenteric coated tablet, a capsule, an enteric coated capsule, a softgelcapsule, or an enteric coated softgel capsule encapsulating iron,folate, and the additives, for example the microparticles, describedherein.

Docosahexaenoic Acid (DHA)

The nutritional compositions described herein include a pharmaceuticallyacceptable phospholipid-DHA derived from eggs and more preferablyinclude organic DHA or DHA derived from organic eggs.

The docosahexaenoic acid described herein generally includes thefollowing formula:

In certain aspects, X can include a phospholipid that is preferablycovalently bonded either directly to the DHA shown in Formula 2 orindirectly (via a saturated or unsaturated lower alkyl linker havingC₁-C₈) to the DHA shown in Formula 2. For example, X can includephosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, orcombinations thereof.

Formula 2 further illustrates the phospholipid being covalently bondedto DHA. In Formula 2, Y can include a primary amine group, a secondaryamine group, a tertiary amine group, a trimethyl amine group, or acombination thereof, and R₁ can include a hydrogen, a hydroxyl group, asaturated or unsaturated alkyl group, an alkoxy group, an omega-3 fattyacid, or any combination thereof. In certain aspects, Y is NH₃ ⁺ orN(CH₃)₃.

In certain aspects, phospholipid-DHA of the nutritional composition mayinclude 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholineor phosphatidylcholine-docosahexaenoic acid (“PC-DHA”),1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine or1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoethanolamineor phosphatidylethanolamine-docosahexaenoic acid (“PE-DHA”), orcombinations thereof. For example, Formula 3 depicts one representativeexample of phosphatidylcholine docosahexaenoic acid.

The docosahexaenoic acids shown in Formulas 1-3 above are preferred overfish oil and algae derived forms of DHA because these docosahexaenoicacids are in the phospholipid form, which aid in docosahexaenoicstability and potency. Furthermore, these forms of DHA are morepalatable to subjects than those derived from fish oil and algaeextracts. Without wishing to be bound by theory, it is thought thatthese forms of DHA are more easily metabolized by a subject and moreeasily cross the blood brain barrier.

FIG. 1 further illustrates this concept. For example, as shown in FIG.1, linolenic acid (i.e., “LNA”) and most forms of docosahexaenoic acidare metabolized in the liver in order to cross the blood brain barrierbefore being used in various metabolic functions in the brain. Forexample, linolenic acid is converted into DHA, and DHA is further bondedto phosphatidylcholine to generate PC-DHA. After synthesizing PC-DHA,liver phospholipase A1 (PLase A1) hydrolyzes PC-DHA to form LysoPC-DHA,which can subsequently pass the blood brain barrier and can be used invarious metabolic functions in the brain such as maintaining neuronalmembrane glycerophospholipids and potentially preventing or reducingapoptosis of glial cells and neurons. As also shown in FIG. 1, if freePC-DHA is present, endothelial lipase can also hydrolyze this freePC-DHA to form LysoPC-DHA, which can also subsequently pass the bloodbrain barrier and be used in various metabolic functions in the brainsuch as maintaining neuronal membrane glycerophospholipids andpotentially preventing or reducing apoptosis glial cells and neurons.

FIG. 2 is an illustration of PC-DHA.

FIG. 3 is an illustration of PE-DHA.

When DHA is covalently linked to phosphatidylethanolamine, these formsof DHA can also similarly be easily converted to DHA forms that cancross the blood brain barrier. For example, without wishing to be boundby theory, PE-DHA can be converted into LysoPC-DHA by various metabolicprocesses and eventually cross the blood brain barrier.

In addition to crossing the blood brain barrier, PC-DHA and PE-DHA canbe used as a polyunsaturated fatty acid nutritional source that crossesthe placental barrier in pregnant mothers and provides a fetus withsufficient DHA amounts for adequate brain and retinal development.

In contrast to the PC-DHA and PE-DHA derived from eggs discussed above,DHA derived from fish oil and algae are primarily covalently bonded totriglycerides that do not include phosphate groups and/or phospholipids.Furthermore, the DHA derived from fish oil and algae often require farmore metabolic steps to be converted into a useful form of DHA that cancross the blood brain barrier and/or the placental barrier.

In certain aspects, the phospholipid extract described herein is presentin a nutritional composition in an amount ranging from 50 mcg to 1000mg.

In certain aspects, the phospholipid extract includes PC-DHA and PE-DHA.In this aspect, the combination of PC-DHA and PE-DHA provided in amicroparticle or a nutritional supplement can be 5% to 15% (by weight)of the overall amount of phospholipid extract in the nutritionalcomposition. In one aspect, PC-DHA can be 50% to 95% of the overallamount of phospholipid DHA in the nutritional composition, and PE-DHAcan be 5% to 45% of the overall amount of DHA in the nutritionalcomposition. The PC-DHA and PE-DHA may also be used in a nutritionalsupplement without the microencapsulation. In one aspect, the at least7.5% the phospholipid extract by weight isphosphatidylcholine-docosahexaenoic acid. And in another aspect, atleast 8% the phospholipid extract by weight isphosphatidylethanolamine-docosahexaenoic acid. Preferably the amount oftriglycerides is low. In one aspect the amount of triglycerides is lessthan 5% of the phospholipid extract, and in another aspect the amount oftriglycerides is less than 3% of the phospholipid extract.

In certain aspects, the DHA described herein includes a ratio of PC-DHAto PE-DHA ranging from 20:1 to 1:1. In another embodiment, the DHAdescribed herein includes a ratio of PC-DHA to PE-DHA ranging from 5:1.

DHA From Eggs

Eggs naturally contain a relatively high about of phospholipids andphospholipid conjugated DHA. Additionally, to increase the amount ofphospholipids and phospholipid conjugated DHA in eggs, chicken feed maybe supplemented with a source of Omega-3 fatty acids like flax seeds, orother sources high in Omega-3. Omega-3 enriched eggs have been shown tohave 39% less Arachidonic Acid, an inflammatory Omega-6 fatty acid thatmost people eat too much of. It has also been shown that Omega-3enriched eggs had 5 times as much Omega-3 as conventional eggs.

Hens that are fed organic chicken feed potentially will be able toproduce DHA, including PC-DHA to PE-DHA, derived from eggs that may belabeled as Organic DHA.

Between 200 mg to 300 mg of usable phospholipid extract for nutritionalsupplementation can be extracted from one egg.

In certain aspects and as discussed further below, the DHA is onlyincluded in the microparticles of the nutritional composition. In otheraspects, a portion of the DHA can be included in the microparticles andanother portion of the DHA can be included in a portion of theencapsulating body (e.g., tablets, softgels, capsules, or chewable) thatis not the microparticle. For example, 90%, 85%, 80%, 75%, 70%, 65%,60%, 55%, or 50% of the overall amount of the DHA can be in themicroparticles and the remainder of DHA can included in a portion of theencapsulating body that is not the microparticle.

Microparticles

Microparticles can be included in the disclosed nutritionalcompositions, and more specifically, the microparticles described hereinare preferably included within a tablet, an enteric coated tablet, acapsule, an enteric coated capsule, a softgel capsule, or an entericcoated softgel capsule.

The microparticles described herein generally include a microparticlecore and a layer or a plurality of layers coated on an outermost surfaceof the microparticle core. The microparticle core is preferably madefrom a pharmaceutically acceptable material that includes, but is notlimited to, tartaric acid, sugar, calcium carbonate, mannitol,microcrystalline cellulose, silica, starch or any combination thereof.These materials are mixed with the phospholipid extract. The egg DHA maybe PC-DHA, PE-DHA, or a mixture. DHA and other omega-3 fatty acids mayalso be incorporated in the microparticle core.

It is preferable that the microparticle cores have a substantiallyrounded shape such that the microparticle cores do not aggregate duringthe production of the microparticles. In addition, because non-roundedshaped microparticle cores tend to aggregate and slow the productionprocess, it is preferable that the microparticle cores have a roundedshape to facilitate production of rounded microparticles.

The microparticle cores described herein can be generally produced withany known extrusion and spheronization techniques that can obtain thedesired microparticle diameters described below. For example, themicroparticle core material can be subjected to radial extrudingprocess, axial extruding process, cone extruding process, dome extrudingprocess, die roller extruding process, or basket extruding process.These materials can be generally extruded through a die or mesh havingvariable sizes. For example, the die and mesh sizes associated withthese extruding techniques can include 200 μm to 8000 μm, 300 μm to 7500μm, 300 μm to 4000 μm, 300 μm to 2000 μm, 400 μm to 2000 μm, 400 μm to1000 μm, and 500 μm to 800 μm to produce microparticle cores having adesired particle diameter. After extrusion, the microparticle corematerials can be further subjected to any known spheronization treatmentto further ensure sufficient microparticle core roundness.

In certain aspects, the microparticle cores can be further subjected toflow cytometry and separated based on desired microparticle coreroundness. For example, in certain aspects, the desired microparticlecore diameter ranges from 180 μm to 425 μm. In exemplary embodiments,the microparticles may have an accumulated volume average particlediameter D50 of from approximately 250 μm to approximately 425 μm tomeet 40-60 mesh requirements. Or the microparticles may have anaccumulated volume average particle diameter D70 of from approximately180 μm to approximately 250 μm to meet 60-80 mesh requirements. Or themicroparticles may have an accumulated volume average particle diameterD90 of from approximately 150 μm to approximately 180 μm to meet 80-100mesh requirements.

In an exemplary embodiment, the microparticle cores may have a volumeaverage particle size distribution index GSDv of approximately 1.30 orless. When GSDv is approximately 1.30 or less, little microparticle coreaggregation occurs and sufficient microparticle roundness can beobtained.

The accumulated volume average particle diameter D50 and the averageparticle size distribution index of the microparticle cores may bemeasured, for example, in the following manner. Based on a particle sizedistribution measured with such a measuring device as Coulter Counter TAII (available from Beckman Coulter, Inc.) or Multisizer II (availablefrom Beckman Coulter, Inc.), accumulated distributions of volume andnumber are each drawn from the small diameter side with respect to thedivided particle size ranges. The particle diameters where theaccumulated value is 16% are designated as volume D_(16V) and numberD_(16P), the particle diameters where the accumulated value is 50% aredesignated as volume D_(50V) and number D_(50P), and the particlediameters where the accumulated value is 84% are designated as volumeD_(84V) and number D_(84P). By using these values, the volume averageparticle size distribution index (GSDv) is calculated as(D_(84V)/D_(16V))^(1/2), and the number average particle sizedistribution index (GSDp) is calculated as (D_(84P)/D_(16P))^(1/2). Themicroparticles may have a shape factor SF1 of from approximately 110 toapproximately 140, and preferably from approximately 120 toapproximately 140, which results in microparticle cores having littleshape irregularity and having sufficient roundness (e.g., sphericalshape).

SF1 is a shape factor that shows the extent of unevenness on the surfaceof the microparticle cores, and is calculated as follows. An opticalmicrograph of the microparticle cores scattered on a glass slide isacquired to a Luzex image analyzer through a video cam, and SF1 iscalculated according to the following expression from the value obtainedby dividing square of the maximum length of the toner particles by theprojected area ((ML)²/A) for 50 toner particles, and the average valuethereof is designated as SF1.SF1=(ML)² /a×n/4×100wherein ML represents the maximum length of the toner particles, and Arepresents the projected area of the particles.

After obtaining microparticle cores having desirable roundness anddiameter, the microparticle cores are then subjected to a coatingprocess in which one or more coating layers are coated on an outermostsurface of the microparticle cores. For example, in certain aspects, anoutermost layer of the microparticle cores are coated with a solution,dispersion, or suspension. In some aspects, the coating may also containadditional DHA derived from eggs described above. In certain aspects,this coating can contain additional components that include, but are notlimited to, excipients.

This coating can partially or completely coat the outermost layer of themicroparticle core. In certain aspects, it is preferable that thecoating completely coats the outermost layer of the microparticle core,and this combination of microparticle core and coating forms themicroparticle. Depending on the type of material used for themicroparticle core, it may be desirable to form an intermediary layerdisposed between the outermost surface of the microparticle core. In oneaspect the coating is pH dependent and may be used for targeting theabsorption at specific locations in the GI tract. In this aspect, theintermediary layer may reduce or prevent the docosahexaenoic acid frominteracting and potentially blocking absorption.

In certain aspects, a plurality of coatings can be provided on themicroparticle core in order to form the desired microparticle. In thisaspect, the microparticle core can be coated with a coating containingDHA derived from eggs on the outermost surface of the microparticlecore. In certain aspects, this coating is allowed to dry at a desiredtemperature and for a desired time period. Next, a second coating can beapplied. In certain aspects, this second coating can include timerelease agents and additional excipients to more slowly and controllablyadminister, for example, the docosahexaenoic acid derived from eggs to asubject. These time release coatings are described in greater detailfurther below. In further embodiments, additional coating layers can beprovided on the microparticle cores.

In certain aspects, it is desirable that the microparticles do notexceed 500 μm in diameter because adverse effects such asgastrointestinal irritation may occur. It is also desirable that themicroparticles have a substantially uniform shape and particle diameterto ensure efficient delivery to the subject. For example, in certainaspects, the microparticles described herein are monodisperse and have apolydispersity index (PDI) ranging from about 1.5 to 1, from about 1.3to 1, and more preferably from about 1.2 to 1.

Organic DHA

The National Organic Program (NOP) under the direction of theAgricultural Marketing Service (AMS), an arm of the United StatesDepartment of Agriculture (USDA) is a national program that establishesnational standards for the production and handling of organicallyproduced products, including a National List of substances approved forand prohibited from use in organic production and handling. NOP iscodified in 7 CFR Part 205, which is incorporated by reference herein.

The final regulation declared that “Producers and handlers ofagricultural products used as ingredients in cosmetics, body careproducts, and dietary supplements could be certified as organicoperations. The ultimate labeling of cosmetics, body care products, anddietary supplements, however, has yet to be addressed.”

The USDA has stated that “There are agricultural products, includingpersonal care products, that, by virtue of their organic agriculturalproduct content, may meet the NOP standards and be labeled as “100percent organic,” “organic” or “made with organic” pursuant to the NOPregulations. Businesses that manufacture and distribute such productsmay be certified under the NOP, and such products may be labeled as “100percent organic,” “organic” or “made with organic” so long as they meetNOP requirements. Additionally, products that may be labeled “100percent organic” or “organic” may also carry the USDA organic seal.”

Except for exempt and excluded operations, each production or handlingoperation or specified portion of a production or handling operationthat produces or handles crops, livestock, livestock products, or otheragricultural products that are intended to be sold, labeled, orrepresented as “100 percent organic,” “organic,” or “made with organic(specified ingredients or food group(s))” must be certified. This meansthat the organic egg farm, the manufacturer of the organic egg DHAmaterial, the intermediate manufacturer, and the final productmanufacturer would need to be certified.

A certified operation must only use allowed substances, methods, andingredients for the production and handling of agricultural productsthat are sold, labeled, or represented as “100 percent organic,” or“organic,” for these products to be in compliance with the Act and theNOP regulations. Use of ionizing radiation, sewage sludge, and excludedmethods are prohibited in the production and handling of organicagricultural products.

The National List identifies synthetic substances, materials andingredients that may be used in organic farming and productionoperations. The List also highlights non-synthetic substances, materialsand ingredients that cannot be used. Notably, microcrystalline celluloseand methyl cellulose, which are ubiquitous excipients in dietarysupplements, are prohibited ingredients. This limitation clearly affectsfinished product manufacturers.

Most DHA and omega fatty acids used in nutritional and dietarysupplements are derived from algae and fish sources. The extractionprocesses are not processes that are eligible to be certified as“organic.” Additionally, some algae sources are genetically modifiedwhich also prevent products derived from the algae as certified“organic.” The present disclosure is the only source of dietarysupplementation of DHA that is able to be certified as “organic” by theUSDA.

Organic egg production is the production of eggs through organic means.There are three main requirements for organic egg production:

-   -   Poultry can be exposed to antibiotics only during infectious        outbreak.    -   Poultry must be fed organic feed (no animal byproducts or        genetically-modified crops).    -   Poultry must have access to outdoors. It cannot be raised in        cages.

Organic production is also regulated by animal welfare audit system.Mistreatment of the chickens could potentially lead a farmer to losinghis organic certification.

Requirements of Phospholipid Extract Intermediate Manufacturers

Phospholipid extract intermediate manufacturers would need to becertified as organic operations.

-   (a) Mechanical or biological methods, including but not limited to    cooking, baking, curing, heating, drying, mixing, grinding,    churning, separating, distilling, extracting, slaughtering, cutting,    fermenting, eviscerating, preserving, dehydrating, freezing,    chilling, or otherwise manufacturing, and the packaging, canning,    jarring, or otherwise enclosing food in a container may be used to    process an organically produced agricultural product for the purpose    of retarding spoilage or otherwise preparing the agricultural    product for market.-   (b) Nonagricultural substances allowed under §205.605 and    non-organically produced agricultural products allowed under    §205.606 may be used:    -   (1) In or on a processed agricultural product intended to be        sold, labeled, or represented as “organic,” pursuant to        §205.301(b), if not commercially available in organic form.    -   (2) In or on a processed agricultural product intended to be        sold, labeled, or represented as “made with organic (specified        ingredients or food group(s)),” pursuant to §205.301(c).-   (c) The handler of an organic handling operation must not use in or    on agricultural products intended to be sold, labeled, or    represented as “100 percent organic,” “organic,” or “made with    organic (specified ingredients or food group(s)),” or in or on any    ingredients labeled as organic:    -   (1) Practices prohibited under paragraphs (e) and (f) of        §205.105.    -   (2) A volatile synthetic solvent or other synthetic processing        aid not allowed under §205.605: Except, That, nonorganic        ingredients in products labeled “made with organic (specified        ingredients or food group(s))” are not subject to this        requirement.

The types of DHA in nutritional supplements currently available are notable to be certified as “organic.” This is because DHA comes from eitherhill and fish, and the extraction processes are not certified asorganic, or it comes from genetically modified algae, which is alsoprohibited from being “organic”.

In one embodiment, this disclosure provide for phospholipids to be usedin a nutritional supplement that may be labeled “organic” according tothe USDA guidelines. In one embodiment, this disclosure provide for DHAto be used in a nutritional supplement that may be labeled “organic”according to the USDA guidelines. In one embodiment, this disclosureprovide for phospholipid-DHA to be used in a nutritional supplement thatmay be labeled “organic” according to the USDA guidelines. “DHA” aslabeled in nutritional supplements oftentimes referred to “DHA” as agenus of various forms of DHA.

Eggs may be farmed following the USDA guidelines for “organic” foods.The phospholipids from the eggs from organically raised and fed hens arethen extracted to be “Organic Phospholipid-DHA,” “Organic DHA,” or“Organic Phospholipids.” Then the Organic phospholipid extract may beincluded in a nutritional supplement in the form of a tablet, capsule,softgel, or chewable tablet.

Folic Acid and Folate

A pharmaceutically acceptable form of folic acid, folic acidderivatives, folate, reduced folate, or any combination thereof isincluded within the nutritional compositions. Folate has been shown toplay a role in nucleotide synthesis in mammals. Specifically, folic acidis known to play a role in various methylation processes in humans andmore specifically in the synthesis of thymine from uracil (i.e., dUMP,deoxyuracil monophosphate). In adult humans, folic acid supplementationhas been implicated in reducing megaloblastic anemia often associatedwith folate deficiency and/or side effects associated with variousmedical treatments (e.g., chemotherapy).

In addition, folic acid has been shown to play a role in preventingneural tube defects that occur during pregnancy. For example, althoughthe molecular and physiological mechanisms are currently unknown, folicacid supplementation has been theorized to reduce the occurrence ofspina bifida by up to 70%. Thus, for at least these reasons, it isdesirable to include a pharmaceutically acceptable form of folic acidand folic acid derivatives in the disclosed nutritional compositions.

Various forms of folic acid are present in high concentrations in eggs.For example, folic acid, reduced folate, dihydrofolate,tetrahydrofolate, 10-formyl folic acid, 5-formyl tetrahydrofolate, and5-methyl tetrahydrofolate are present in egg yolks. Therefore, incertain aspects and to potentially lower production costs of thedisclosed nutritional compositions, it is desirable to extract folatefrom eggs while obtaining the phospholipid derived from eggs.

In certain aspects, folic acid derivatives having substituents at its N⁵or N¹⁰ position have increased stability and are less prone to cleavageand oxidation. Thus, these folic acid derivatives may be favored in thedisclosed nutritional composition. For example, in certain aspects, itis preferable that at least one of folic acid, 10-formyl folic acid,5-formyl tetrahydrofolate, 5-methyl tetrahydrofolate, or any combinationthereof is present at a higher concentration in the nutritionalcomposition than dihydrofolate and tetrahydrofolate, and in certainaspects, dihydrofolate and/or tetrahydrofolate are not present in thenutritional composition.

The total biologically active amount of folate: folic acid andderivatives thereof present in the nutritional composition ranges from100 μg to 15 mg. Total biologically active amounts of folic acid andderivatives thereof below 100 μg are potentially inadequate to preventor reduce problems associated with folate deficiencies (e.g.,megaloblastic anemia, neural tube defects in fetuses, etc.). Pregnantmothers are recommended to take between 400 mcg and 1 mg of folate. Highdosages of folate have been shown to improve a number of human ailmentsand conditions including impaired cognitive function, memory loss,diabetic peripheral neuropathy, and depression. Therefore, in certainaspects, the total biologically active amount of folic acid andderivatives thereof present in the nutritional composition ranges from100 μg to 15 mg, 400 μg to 800 μg, 400 μg to 1000 μg, 800 μg to 1000 μg,1 mg to 3 mg, 3 mg to 6 mg, 7.5 mg to 15 mg, or any range havingendpoints falling within any of the preceding ranges.

In certain aspects, the total amount of folate, folic acid, and reducedfolate derivatives present in the nutritional composition ranges from0.1 mg to 20 mg based on the total weight of the nutritionalcomposition.

In certain aspects, the folic acid and folic acid derivatives are notincluded in the microparticles of the nutritional composition. In otheraspects, a portion of the folic acid and folic acid derivatives areincluded in any of the coated layers of the microparticles and anotherportion of the folic acid and folic acid derivatives are included in theencapsulating body (e.g., tablets and capsules) that is not themicroparticle. For example, in certain aspects, at least 90%, 85%, 80%,75%, 70%, 65%, 60%, 55%, or 50% of the overall amount of the folic acidand folic acid derivatives are not in the microparticles, and in thisaspect, the remainder of the folic acid and folic acid derivatives canincluded in the microparticle.

Iron

A pharmaceutically acceptable form of iron is also included within thedisclosed nutritional compositions. In the human body, iron is a keycomponent, which is often complexed with various porphyrin rings tofacilitate numerous metabolic and biological processes. Morespecifically, iron is often complexed with heme groups to formhemoglobin, and iron is also often complexed with various cytochromes(e.g., Cytochrome C in the mitochondria) to carry out electron transportduring the production of adenosine tri-phosphate (i.e., ATP) in themitochondria.

In humans, iron deficiency is usually associated with various anemias,thrombocytosis, decreased immunity, increased susceptibility to sepsis,increased maternal mortality, and atrophy of mucous membranes (e.g.,Plummer-Vinson syndrome). Furthermore, iron deficiency in pregnantmothers, can potentially lead to low birth weights, preterm birth, andunder development in a newborn child. Thus, for at least these reasons,it is desirable to include a pharmaceutically acceptable form of iron inthe disclosed nutritional compositions.

In the disclosed nutritional composition, it is preferable to includeiron in the total amount of about 0.1 mg/kg to 6 mg/kg, 2.5 mg/kg to 5.5mg/kg, 3 mg/kg to 5 mg/kg, 3.5 mg/kg to 4.5 mg/kg, or any range havingendpoints falling within any of the preceding ranges of a subject's bodymass. For example, if the subject has a body mass of 100 kg (i.e., 220lbs), it is preferable to orally administer 10 mg to 600 mg of iron tothis subject when using the 2 mg/kg to 6 mg/kg range. Total amounts ofiron in the nutritional composition falling below 1 mg/kg arepotentially inadequate to prevent or reduce problems associated withiron deficiency. Furthermore, total amounts of iron exceeding 6 mg/kgmay be associated with unwanted side effects associated such as ironpoisoning if administered for an extended period of time. Therefore, incertain aspects, the total amount of iron thereof present in thenutritional composition ranges from 10 mg to 600 mg, 10 mg to 500 mg, 10mg to 400 mg, 10 mg to 300 mg, 10 mg to 200 mg, 10 mg to 100 mg, 50 mgto 500 mg, 50 mg to 400 mg, 50 mg to 300 mg, 50 mg to 200 mg, 50 mg to100 mg, 100 mg to 500 mg, 100 mg to 450 mg, 100 mg to 400 mg, 100 mg to350 mg, 100 mg to 300 mg, 100 mg to 250 mg, 100 mg to 200 mg, 100 mg to150 mg, 200 mg to 400 mg, 200 mg to 350 mg, 200 mg to 300 mg, 200 mg to250 mg, 300 mg to 500 mg, 300 mg to 450 mg, 300 mg to 400 mg, 300 mg to350 mg, or any range having endpoints falling within any of thepreceding ranges.

Iron may be provided through many different pharmaceutically acceptablesalts or chelates and one skilled in the art would know of these saltsand chelates. Some pharmaceutically acceptable forms of ironsupplementation may be through carbonyl, ferrous gluconate, ferrousfumerate, iron amino acid complexes, ferronyl carbonate, iron chelates,among others not listed.

In certain aspects, the total amount of Iron present in the nutritionalcomposition is about 27.5 mg. In certain aspects, the total amount ofiron present in the nutritional composition ranges from 0.5 mg to 100 mgbased on the total weight of the nutritional composition.

In certain aspects, iron is not included in the microparticles of thenutritional composition. In other aspects, a portion of iron is includedin any of the coated layers of the microparticles and another portion ofiron is included in the encapsulating body (e.g., tablets and capsules)that is not the microparticle. For example, in certain aspects, at least90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or 50% of the overall amount ofiron is not in the microparticles, and in this aspect, the remainder ofthe iron can be included the microparticle.

Other Ingredients

In certain embodiments and as discussed further below, the disclosednutritional composition can optionally include pharmaceuticallyacceptable Vitamin B₆, Vitamin B₁₂, N-Acetyl-Cysteine (NAC), CoenzymeQ10 (CoQ 10) or any combination thereof.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin B₆. Vitamin B₆,and more specifically pyridoxal-5-phosphate, is involved in numerousbiological reactions occurring in a subject including amino acidmetabolism, hemoglobin synthesis, neurotransmitter synthesis, lipidmetabolism, and gluconeogenesis (e.g., glycogenolysis). Vitamin B₆ mayalso be supplemented as pyridoxine HCl. Other forms of Vitamin B₆ areknown and one skilled in the art would be aware of the various forms.Thus, to further complement the effects of DHA, folic acid andderivatives thereof, and iron mentioned above, Vitamin B₆ can be addedto the nutritional composition. In certain aspects, the total amount ofVitamin B₆ present in the nutritional composition ranges from 0.1 mg to100 mg, 0.1 mg to 75 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 10mg, 0.1 mg to 7.5 mg, 0.1 mg to 5 mg, 0.1 mg to 3 mg, 0.1 mg to 2.5 mg,0.1 mg to 2 mg, 0.1 mg to 1 mg, 0.1 mg to 0.5 mg, 0.2 mg to 10 mg, 0.2mg to 7.5 mg, 0.2 mg to 5 mg, 0.2 mg to 2.5 mg, 0.2 mg to 2.0 mg, 0.2 mgto 1.5 mg, 0.2 mg to 1 mg, 0.3 mg to 10 mg, 0.3 mg to 7.5 mg, 0.3 mg to5 mg, 0.3 mg to 2.5 mg, 0.3 mg to 2.0 mg, 0.3 mg to 1.5 mg, 0.3 mg to 1mg, 0.5 mg to 5 mg, 0.5 mg to 4 mg, 0.5 mg to 3 mg, 0.5 mg to 2.5 mg,0.5 mg to 2.0 mg, 0.5 mg to 1.5 mg, 0.5 mg to 1 mg, 0.75 mg to 3 mg,0.75 mg to 2.5 mg, 0.75 mg to 2.0 mg, 0.75 mg to 1.5 mg, 0.75 mg to 1mg, 1 mg to 2 mg, 1 mg to 1.5 mg or any range having endpoints fallingwithin any of the preceding ranges.

In certain aspects, the total amount of Vitamin B₆ present in thenutritional composition ranges from 0.5 mg to 55 mg based on the totalweight of the nutritional composition. In one aspect, the total amountof Vitamin B₆ is 26 mg. In another aspect, the total amount of VitaminB₆ is 35 mg. In one aspect, the total amount of Vitamin B₆ is 25 mg.

In certain aspects, Vitamin B₆ is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Vitamin B₆is included in any of the coated layers of the microparticles andanother portion of Vitamin B₆ is included in the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Vitamin B₆ is not in the microparticles,and in this aspect, the remainder of Vitamin B₆ can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin B₁₂. Vitamin B₁₂plays a role in DNA synthesis, regulation of DNA synthesis, and fattyacid synthesis. Vitamin B₁₂ has been implicated in playing a key role inmaintaining normal brain function and regulating the nervous system. Inhumans, Vitamin B₁₂ deficiency can cause severe and irreversible damageto the brain and nervous system, which may manifest with symptoms ofmania and psychosis. Thus, to potentially prevent Vitamin B₁₂ deficiencyand to further complement the effects of DHA, folic acid and derivativesthereof, and iron discussed above, Vitamin B₁₂ can be added to thenutritional composition. Vitamin B₁₂ may also be supplemented ascyanocobalamin, or preferably methylcobalamin. Other forms of VitaminB₁₂ are known and one skilled in the art would be aware of the variousforms.

In certain aspects, the total amount of Vitamin B₁₂ present in thenutritional composition ranges from 0.1 μg to 5 μg, 0.1 μg to 4 μg, 0.1μg to 3 μg, 0.1 μg to 2 μg, 0.1 μg to 1 μg, 0.3 μg to 4.5 μg, 0.3 μg to3.5 μg, 0.3 μg to 2.5 μg, 0.3 μg to 2 μg, 0.3 μg to 1 μg, 0.4 μg to 3.5μg, 0.4 μg to 3 μg, 0.4 μg to 2.5 μg, 0.4 μg to 2 μg, 0.4 μg to 1 μg,0.5 μg to 3 μg, 0.5 μg to 2.5 μg, 0.5 μg to 2 μg, 0.5 μg to 2 μg, 0.5 μgto 0.9 μg, or any range having endpoints falling within any of thepreceding ranges. In certain aspects, the total amount of Vitamin B₁₂present in the nutritional composition ranges from 10 μg to 5 mg basedon the total weight of the nutritional composition. In one aspect, thetotal amount of Vitamin B₁₂ is 12 mcg. In another aspect, the totalamount of Vitamin B₁₂ is 2 mg.

In certain aspects, Vitamin B 12 is not included in the microparticlesof the nutritional composition. In other aspects, a portion of VitaminB₁₂ is included in any of the coated layers of the microparticles andanother portion of Vitamin B₁₂ is included in a portion of theencapsulating body (e.g., tablets and capsules) that is not themicroparticle. For example, in certain aspects, at least 90%, 85%, 80%,75%, 70%, 65%, 60%, 55%, or 50% of the overall amount of Vitamin B₁₂ isnot in the microparticles, and in this aspect, the remainder of VitaminB₁₂ can be included in the microparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable N-Acetyl-Cysteine in therange of from 100 mg to 1000 mg, 100 mg to 900 mg, 100 mg to 800 mg, 100mg to 700 mg, 100 mg to 600 mg, 100 mg to 500 mg, 100 mg to 400 mg, 100mg to 300 mg, 100 mg to 200 mg, 200 mg to 800 mg, 200 mg to 650 mg, 200mg to 500 mg, 200 mg to 450 mg, 200 mg to 300 mg, 300 mg to 750 mg, 300mg to 600 mg, 300 mg to 500 mg, 300 mg to 450 mg, 300 mg to 400 mg, 400mg to 650 mg, 400 mg to 600 mg, 400 mg to 550 mg, 400 mg to 500 mg, 400mg to 450 mg, or any range having endpoints falling within any of thepreceding ranges.

In certain aspects, the total amount of N-Acetyl-Cysteine present in thenutritional composition ranges from 1 mg 1 g based on the total weightof the nutritional composition.

In certain aspects, N-Acetyl-Cysteine is not included in themicroparticles of the nutritional composition. In other aspects, aportion of N-Acetyl-Cysteine is included in any of the coated layers ofthe microparticles and another portion of N-Acetyl-Cysteine is includedin a portion of the encapsulating body (e.g., tablets and capsules) thatis not the microparticle. For example, in certain aspects, at least 90%,85%, 80%, 75%, 70%, 65%, 60%, 55%, or 50% of the overall amount ofN-Acetyl-Cysteine is not in the microparticles, and in this aspect, theremainder of N-Acetyl-Cysteine can be included in the microparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Coenzyme Q10 (CoQ 10).CoQ 10 is a vitamin-like substance that is present primarily inmammalian mitochondria. In humans, CoQ10 has been implicated inoxidative phosphorylation and electron chain transport in themitochondria, which ultimately results in the production of ATP.Furthermore, CoQ10 has an antioxidant function that reduces or preventslipid peroxidation. Therefore, in certain aspects, CoQ10 may actsynergistically with the DHA described herein as well as Vitamin B₆and/or Vitamin B₁₂ to promote cognitive function by promoting lipidsynthesis and lipid maintenance occurring, for example, in the brainwhile concurrently reducing lipid damage occurring from lipidperoxidation.

In certain aspects, the total amount of CoQ10 present in the nutritionalcomposition ranges from 0.5 mg to 7 mg, 0.5 mg to 6 mg, 0.5 mg to 5 mg,0.5 mg to 4 mg, 0.5 mg to 3 mg, 0.5 mg to 2 mg, 0.5 mg to 1 mg, 1 mg to6.5 mg, 1 mg to 6 mg, 1 mg to 5.5 mg, 1 mg to 5 mg, 1 mg to 4.5 mg, 1 mgto 4 mg, 1 mg to 3.5 mg, 1 mg to 3 mg, 1 mg to 2.5 mg, 1 mg to 2 mg, 2mg to 6 mg, 2 mg to 5.5 mg, 2 mg to 5 mg, 2 mg to 4.5 mg, 2 mg to 4 mg,2 mg to 3.5 mg, 2 mg to 3 mg, 2 mg to 2.5 mg, 3 mg to 6 mg, 3 mg to 5.5mg, 3 mg to 5 mg, 3 mg to 4.5 mg, 3 mg to 4 mg, 3 mg to 3.5 mg, 4 mg to5.5 mg, 4 mg to 5 mg, 4 mg to 4.5 mg, or any range having endpointsfalling within any of the preceding ranges. In certain aspects, thetotal amount of CoQ10 present in the nutritional composition ranges from50 mg to 200 mg based on the total weight of the nutritionalcomposition.

In certain aspects, CoQ10 is not included in the microparticles of thenutritional composition. In other aspects, a portion of CoQ10 isincluded in any of the coated layers of the microparticles and anotherportion of CoQ10 is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of CoQ10 is not in the microparticles, and inthis aspect, the remainder of CoQ10 can be included in a portion of theencapsulating body that is not the microparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin C in the range offrom 10 mg to 1000 mg.

In certain aspects, the total amount of Vitamin C present in thenutritional composition is about 70 mg.

In certain aspects, Vitamin C is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Vitamin C isincluded in any of the coated layers of the microparticles and anotherportion of Vitamin C is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Vitamin C is not in the microparticles, andin this aspect, the remainder of Vitamin C can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin D in the range offrom 50 IU to 2000 IU.

In certain aspects, the total amount of Vitamin D present in thenutritional composition is about 1000 IU.

In certain aspects, Vitamin D is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Vitamin D isincluded in any of the coated layers of the microparticles and anotherportion of Vitamin D is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Vitamin D is not in the microparticles, andin this aspect, the remainder of Vitamin D can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin E in the range offrom 10 IU to 1000 IU.

In certain aspects, the total amount of Vitamin E present in thenutritional composition is about 10 IU.

In certain aspects, Vitamin E is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Vitamin E isincluded in any of the coated layers of the microparticles and anotherportion of Vitamin E is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Vitamin E is not in the microparticles, andin this aspect, the remainder of Vitamin E can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Vitamin C in the range offrom 10 mg to 1000 mg.

In certain aspects, the total amount of Vitamin C present in thenutritional composition is about 70 mg.

In certain aspects, Vitamin C is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Vitamin C isincluded in any of the coated layers of the microparticles and anotherportion of Vitamin C is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Vitamin C is not in the microparticles, andin this aspect, the remainder of Vitamin C can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Calcium in the range offrom 5 mg to 200 mg. Calcium may be provided through many differentpharmaceutically acceptable salts and one skilled in the art would knowof these salts.

In certain aspects, the total amount of Calcium present in thenutritional composition is about 15 mg.

In certain aspects, Calcium is not included in the microparticles of thenutritional composition. In other aspects, a portion of Calcium isincluded in any of the coated layers of the microparticles and anotherportion of Calcium is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Calcium is not in the microparticles, andin this aspect, the remainder of Calcium can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally include pharmaceutically acceptable Iodine in the range offrom 50 mcg to 300 mcg. Iodine may be provided through many differentpharmaceutically acceptable salts and one skilled in the art would knowof these salts. In one aspect, iodine is provided as potassium iodide.

In certain aspects, the total amount of Iodine present in thenutritional composition is about 150 mcg.

In certain aspects, Iodine is not included in the microparticles of thenutritional composition. In other aspects, a portion of Iodine isincluded in any of the coated layers of the microparticles and anotherportion of Iodine is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Iodine is not in the microparticles, and inthis aspect, the remainder of Iodine can be included in themicroparticle.

In certain embodiments, the disclosed nutritional composition canoptionally included pharmaceutically acceptable Magnesium in the rangeof from 5 mg to 100 mg. Magnesium may be provided through many differentpharmaceutically acceptable salts and one skilled in the art would knowof these salts. In one aspect, magnesium is provided as magnesium oxide.

In certain aspects, the total amount of Magnesium present in thenutritional composition is about 20 mg.

In certain aspects, Magnesium is not included in the microparticles ofthe nutritional composition. In other aspects, a portion of Magnesium isincluded in any of the coated layers of the microparticles and anotherportion of Magnesium is included in a portion of the encapsulating body(e.g., tablets and capsules) that is not the microparticle. For example,in certain aspects, at least 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or50% of the overall amount of Magnesium is not in the microparticles, andin this aspect, the remainder of Magnesium can be included in themicroparticle.

In addition, any standard pharmaceutically acceptable excipient can beused in the nutritional composition. For example, these excipients caninclude diluents (e.g., mannitol, sorbitol, lactose, sucrose, andcompressible sugars such as DiPac™ (dextrinized sucrose), available fromAustin Products Inc., Holmdel, N.J.), splitting or swelling agents(e.g., polyvinyl polypyrrolidone, croscarmellose sodium (e.g.,Ac-Di-Sol™ available from FMC BioPolymer, Philadelphia, Pa.), starchesand derivatives, cellulose and derivatives, microcrystalline celluloses,such as Avicel™ PH 101 or Avicel™ CE-15 (a microcrystalline modifiedwith guar gum), both available from FMC BioPolymer, Philadelphia, Pa.),lubricating agents (e.g., magnesium stearate), and flow agents (e.g.,colloidal silicon dioxide, such as Cab-O-Sil M5 available from CabotCorporation, Kokomo, Ind.).

Also, sweeteners can be included in the nutritional compositionsdescribed herein. For example, sweeteners can be used to impart apleasant flavor to the composition. Suitable sweeteners for use in thepresent disclosure include natural sweeteners such as sucrose, dextrose,fructose, invert sugar, mannitol, sorbitol, and the like, as well assynthetic sweeteners such as saccharin, aspartame, acesulfame potassium,cyclamates, and other commercial artificial sweeteners well-known tothose of skill in the art. A preferred sweetener is acesulfame K(Sunett™ available from Nutrinova, Frankfort, Germany). The sweetener isadded in an amount to achieve a desired sweetness. Typically, thesweetener is present in an amount from about 1.0 wt % to about 5.0 wt %of the overall weight of the nutritional composition. Since thenutritional supplement may capitalize on the DHA being sourced fromeggs, egg-friendly flavors are also preferred, which include vanilla anddulce de leche or caramel. Other flavors as chocolate or strawberry arealso workable. Those skilled in the part will appreciate that the amountof sweetener may vary depending on the strength of the particularsweetener used and the levels approved by the regulatory authorities foruse in pharmaceutical products.

Time Release Coatings

In certain aspects, the outermost surface of the encapsulating body andthe outermost surface of the microparticle can independently include atime release coating. For example, in certain aspects the outermostsurface of the encapsulating body can include a time release coatingwhile such a coating is omitted from the microparticle. In otheraspects, the outermost surface of the microparticle can include a timerelease coating while such a coating is omitted from the outermostsurface of the encapsulating body.

Examples of these time release agents can include but are not limited tohydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropylmethyl cellulose phthalate, pullulan, gelatin, collagen, casein, agar,gum arabic, dextrin, ethyl cellulose, methyl cellulose, chitin,chitosan, mannan, carboxymethylethyl cellulose, sodium carboxymethylcellulose, polyethylene glycol, sodium alginate, poly(vinyl alcohol),cellulose acetate, poly(vinylpyrrolidone), silicone, poly(vinyl acetal)diethylamino acetate, albumin, adenine, cystine, D-tyrosine, or anycombination thereof.

In certain aspects, these time release coatings may range from 1-15% ofthe overall weight of the nutritional composition.

EXAMPLES Example 1 (Microparticles Coated with Phospholipid Extract)

Microparticle cores can be prepared by extrusion spheronizer technology,and the microparticle cores can be subsequently made of phospholipidextract, cellulose, starch, lactose, mannitol. DHA may comprise 25% to50% of the microparticle core.

A pharmaceutically acceptable source of phospholipid extract may bemixed with a pharmaceutically acceptable neutral material such astartaric acid, sugar sphere, calcium carbonate, mannitol,microcrystalline cellulose, silica, or starch which is then subjected toan extruding step to obtain microparticle cores in which 95% of themicroparticle cores have an average particle diameter ranging from 90 μmto 500 um. These materials are mixed for 15-25 minutes and then extrudedout an extruder.

Next, the microparticle cores are placed into a spheroidizer at 500 rpmfor 5 to 10 second to ensure that sufficient microparticle coreroundness is obtained.

After ensuring proper microparticle core roundness has been obtained,the microparticle cores are organized into a bed of microparticle coresthat are subjected to a coating step. Next, the microparticle cores mayalso be (i) directly coated with an enteric coating to provide adissolution rate profile and/or (ii) directly coated with a protectivecoating: solution, suspension, or dispersion or. The enteric coating maybe L30D on different polymers. The enteric coating may comprise 1-5% ofthe weight of the total microparticle composition. The protectivecoating maybe hpmc. The protective coating may comprise 1-10% of theweight of the total microparticle composition.

Example 2 (Exemplary Nutritional Composition Formulations)

Table 1 lists exemplary formulations of the nutritional composition ofthe present disclosure.

TABLE 1 Exemplary Exemplary Exemplary Exemplary Formulation 1Formulation 2 Formulation 3 Formulation 4 Ingredient (wt %) (wt %) (wt%) (wt %) Total Egg Phospholipid 200 mg 90-95 mg 90-95 mg 90-95 mg(“Phospholipid extract”) PC-DHA 20 mg 9 mg 9 mg 9 mg PE-DHA 5 mg 4.5 mg4.5 mg 4.5 mg Folic Acid or other folate 700 mcg 3 mg 6 mg 15 mg (totalfolate) Iron 27.5 mg 0 mg 0 mg 0 mg Vitamin B6 (any form) 26 mg 35 mg 0mg 0 mg Vitamin E 20 IU 0 mg 0 mg 0 mg Vitamin B12 (any form) 12 mcg 2mg 2 mg 0 mg Calcium 15 mg 0 mg 0 mg 0 mg NAC (any form) 2.5 mg 0 mg 600mg 0 mg The formulations above do not include excipients, binders,stabilizers, etc.

The foregoing description provides embodiments of the disclosure by wayof example only. It is envisioned that other embodiments may performsimilar functions and/or achieve similar results. Any and all suchequivalent embodiments and examples are within the scope of the presentdisclosure and are intended to be covered by the appended claims

It should be emphasized that the embodiments described herein are merelypossible examples of implementations, merely set forth for a clearunderstanding of the principles of the present disclosure. Manyvariations and modifications may be made to the described embodiment(s)without departing substantially from the spirit and principles of thepresent disclosure. Further, the scope of the present disclosure isintended to cover any and all combinations and sub-combinations of allelements, features, and aspects discussed above. All such modificationsand variations are intended to be included herein within the scope ofthe present disclosure, and all possible claims to individual aspects orcombinations of elements or steps are intended to be supported by thepresent disclosure.

One should note that conditional language, such as, among others, “can,”“could,” “might,” or “may,” unless specifically stated otherwise, orotherwise understood within the context as used, is generally intendedto convey that certain embodiments include, while alternativeembodiments do not include, certain features, elements and/or steps.Thus, such conditional language is not generally intended to imply thatfeatures, elements and/or steps are in any way required for one or moreparticular embodiments or that one or more particular embodimentsnecessarily include logic for deciding, with or without user input orprompting, whether these features, elements and/or steps are included orare to be performed in any particular embodiment. Unless statedotherwise, it should not be assumed that multiple features, embodiments,solutions, or elements address the same or related problems or needs.

Various implementations described in the present disclosure may includeadditional systems, methods, features, and advantages, which may notnecessarily be expressly disclosed herein but will be apparent to one ofordinary skill in the art upon examination of the following detaileddescription and accompanying drawings. It is intended that all suchsystems, methods, features, and advantages be included within thepresent disclosure and protected by the accompanying claims.

What is claimed is:
 1. A composition, comprising: a phospholipid extractat a concentration ranging from 50 mg to 600 mg, the phospholipidextract having phosphatidylcholine-docosahexaenoic acid andphosphatidylethanolamine-docosahexaenoic acid at a ratio ranging fromabout 1:1 to about 3:1, and an effective amount of stabilizer thatimproves shelf life.
 2. The composition of claim 1, additionallycomprising: an amount of folic acid, an amount of Vitamin D, an amountof Vitamin B₆, an amount of Vitamin B₁₂, an amount of Vitamin E, anamount of Vitamin C, an amount of Iodine between, an amount of Ironbetween, and an amount of Magnesium.
 3. The composition of claim 2,wherein the amount of phospholipid extract is 200 mg.
 4. The compositionof claim 2, wherein the amount of phospholipid-DHA is 99 mg.
 5. Thecomposition of claim 2, wherein the amount of folic acid is between 400mcg and 800 mcg, the amount of Vitamin D is between 100 IU and 2000 IU,the amount of Vitamin B₆ is between 0.5 mg and 50 mg, the amount ofVitamin B₁₂ is between 10 mcg and 1 mg, the amount of Vitamin E isbetween 10 IU and 100 IU, the amount of Vitamin C is between 50 mg and150 mg, the amount of Iodine is between 50 mcg and 300 mcg, the amountof Iron is between 10 mg and 30 mg, and the amount of Magnesium isbetween 5 mg and 100 mg.
 6. The composition of claim 5, wherein theamount of folic acid is 400 mcg, the amount of Vitamin D is 1000 IU, theamount of Vitamin B₆ is 26 mg, the amount of Vitamin B₁₂ is 13 mcg, theamount of Vitamin E is 10 IU, the amount of Vitamin C is 60 mg, theamount of Iodine is 150 mcg, the amount of Iron is 18 mg, and the amountof Magnesium is 25 mg.
 7. The composition of claim 5, wherein the amountof folic acid is 800 mcg, the amount of Vitamin D is 1000 IU, the amountof Vitamin B₆ is 5 mg, the amount of Vitamin B₁₂ is 1.9 mg, the amountof Vitamin E is 20 IU, the amount of Vitamin C is 70 mg, the amount ofIodine is 150 mcg, the amount of Iron is 27 mg, and the amount ofMagnesium is 7.5 mg.
 8. The composition of claim 7, wherein thephospholipid extract contains less than 3%, by weight, triglycerides. 9.The composition of claim 1, wherein the amount of phospholipid extractis about 150 mg.
 10. The composition of claim 1, wherein the amount ofphospholipid-DHA is 74 mg.
 11. The composition of claim 1, wherein thecomposition is a capsule or softgel.
 12. The composition of claim 1,wherein the phospholipid extract contains less than 3%, by weight,triglycerides.
 13. The composition of claim 1, wherein the amount ofphosphatidylcholine-docosahexaenoic acid makes up at least 7.5% of thephospholipid extract and phosphatidylethanolamine-docosahexaenoic acidmakes up at least 8% of the phospholipid extract.
 14. A method ofproviding a human a source of omega-3 fatty acids, the methodcomprising: administering to the human a composition comprising: aphospholipid extract at a concentration ranging from 50 mg to 600 mg,the phospholipid extract having phosphatidylcholine-docosahexaenoic acidand phosphatidylethanolamine-docosahexaenoic acid at a ratio rangingfrom about 1:1 to about 3:1, and an effective amount of stabilizer thatimproves shelf life.
 15. The method of claim 14, wherein the amount ofphospholipid extract is 150 mg.
 16. The method of claim 14, wherein theamount of phospholipid-DHA is 15 mg.
 17. The method of claim 14, whereinthe human is administered the composition more than once a day.
 18. Amethod of providing a pregnant or nursing mother a source of omega-3fatty acids, the method comprising: administering to the human acomposition comprising: a phospholipid extract at a concentrationranging from 50 mg to 600 mg, the phospholipid extract havingphosphatidylcholine-docosahexaenoic acid andphosphatidylethanolamine-docosahexaenoic acid at a ratio ranging fromabout 1:1 to about 3:1, and an effective amount of stabilizer thatimproves shelf life.
 19. The method of claim 18, wherein the compositionadditionally comprises: an amount of folic acid that is between 400 mcgand 800 mcg, an amount of Vitamin D is between 100 IU and 2000 IU, anamount of Vitamin B₆ is between 0.5 mg and 50 mg, an amount of VitaminB₁₂ is between 10 mcg and 1 mg, an amount of Vitamin E between 10 IU and100 IU, an amount of Vitamin C between 50 mg and 150 mg, an amount ofIodine between 50 mcg and 300 mcg, an amount of Iron is between 10 mgand 30 mg, and an amount of Magnesium between 5 mg and 30 mg.
 20. Themethod of claim 19, wherein the amount of folic acid is 400 mcg, theamount of Vitamin D is 1000 IU, the amount of Vitamin B₆ is 26 mg, theamount of Vitamin B₁₂ is 13 mcg, the amount of Vitamin E is 10 IU, theamount of Vitamin C is 60 mg, the amount of Iodine is 150 mcg, theamount of Iron is 18 mg, and the amount of Magnesium is 25 mg.